Therapeutic augmentation of collateral artery growth (arteriogenesis) is of tremendous clinical interest. Since monocytes home to areas of arteriogenesis and create a local arteriogeneic milieu by secreting a wide range of growth factors, we followed the idea of utilizing these cells for augmentation of collateral growth. For that purpose, we adoptively transferred both syngeneic (same strain) and allogeneic (different strain) bone marrow derived monocytes (BMDMs) into balb/c mice 24 h after femoral artery ligation. Restoration of hind-limb perfusion was determined by Laser Doppler Perfusion Imaging and histological workup. While syngeneic cell transplantation did not augment arteriogenesis in comparison to non-transplanted animals (PI = 0.56 ± 0.06 vs. 0.48 ± 0.09, respectively, ns), allogeneic monocytes massively promoted the collateralization (PI = 0.85 ± 0.14, p < 0.001). Homed monocytes were visualized near growing collateral vessels by staining the cells with the lipophil fluorochrome DiI prior to transplantation. To analyze whether the effect of allogeneic BMDM transplantations is due to local inflammation triggered by a host-versus-graft reaction, transplant recipients were pre-treated with the immunosuppressive drug cyclosporine A, which completely prevented the effect of allogeineic monocyte transplantation (PI = 0.45 ± 0.06, p < 0.001). Here, we have demonstrated murine allogeneic monocytes to be an attractive way to trigger local inflammatory responses near growing collateral vessels and stimulate their adaption, overcoming the endogenous restriction of collateral vessel growth.

Bajenaru L.,Polytechnic University of Bucharest | Berger D.,Polytechnic University of Bucharest | Miclea L.,Carol Davila University of Medicine and Pharmacy | Miclea L.,Herzzentrum Dresden Gmbiversitatsklinik | And 5 more authors.Journal of Biomedical Materials Research - Part A | Year: 2014

Calcified aortic stenosis is the predominant valve disease in the western world. Currently, surgical aortic valve replacement is the gold standard procedure for symptomatic severe aortic stenosis that can be performed with low morbidity and mortality. The prevalence of aortic stenosis increases with age, and the incidence of several comorbidities also unavoidably elevates the risk of surgical treatment. Therefore, the most adequate and gentle treatment is needed especially for this population. Since the first transcatheter aortic valve implantation (TAVI) was performed in 2002, the main implanting routes are the transfemoral, retrograde access through the common femoral artery, and the antegrade, transapical approach via anterolateral minithoracotomy. Meanwhile, TAVI has become an alternative treatment for patients who are not suitable candidates for surgical therapy in some centers.The initial clinical results are promising and have confirmed the feasibility of this technique. Due to the restricted long-term data, conventional aortic valve replacement still remains the standard for the treatment of aortic stenosis. Selection of the suitable therapy approach (surgical replacement, transfemoral or transapical aortic valve implantation) must consider each patients specific risk profile and individual indication. Prospective, randomized trials will be necessary to assess the individual survival benefit of TAVI for various risk populations and to extend the indication.